Methods for making oral compositions

ABSTRACT

Disclosed are oral compositions which are effective against plaque and gingivitis and contain a noncationic water insoluble antibacterial agent.

This is a continuation of application Ser. No. 07/900,640, filed on Jun.18, 1992, now U.S. Pat. No. 5,290,541.

TECHNICAL FIELD

The present invention relates to oral compositions which provideantiplaque and antigingivitis benefits as well as being effectiveagainst other anaerobic infections of the mouth.

Plaque induced diseases, including periodontitis and gingivitis, arebelieved to involve anaerobic bacterial infections. Periodontal diseaseaffects the periodontium, which is the investing and supporting tissuesurrounding a tooth (i.e., the periodontal ligament, the gingiva, andthe alveolar bone). Gingivitis and periodontitis are inflammatorydisorders of the gingiva and the periodontal ligament, respectively.Gingivosis and periodontosis are more severe conditions involvingdegenerative disorders of the tissue. Combinations of inflammatory anddegenerative conditions are termed periodontitis complex.

Periodontal disease is a major cause of tooth loss in adults. Tooth lossfrom periodontal disease is a significant problem beginning at age 35,but even by age 15 it is estimated that about 4 out of 5 persons alreadyhave gingivitis and 4 out of 10 have periodontitis.

While good oral hygiene, as achieved by brushing the teeth with acleansing dentifrice, may help reduce the incidence of periodontaldisease, it does not necessarily prevent or eliminate its occurrence.This is because microorganisms contribute to both the initiation andprogress of periodontal disease. Thus, in order to prevent or treatperiodontal disease, these microorganisms must be suppressed by somemeans other than simple mechanical scrubbing. Towards this end, therehas been a great deal of research aimed at developing therapeuticdentifrices, mouthwashes, and methods of treating periodontal diseasewhich are effective in suppressing these microorganisms.

The use of noncationic, water-insoluble antibacterial agents in oralproducts is disclosed in a number of references. One such reference isU.S. Pat. No. 4,022,889 to Vinson et al. Vinson describes compositionscontaining zinc salts and antibacterial agents such as halogenatedsalicylanilides and halogenated hydroxydiphenyl ethers.

Another reference disclosing noncationic water-insoluble antibacterialagents is U.K. Patent Application GB 2,200,551, published Aug. 10, 1988.In addition to the antibacterial, the compositions contain a molecularlydehydrated polyphosphate salt. The salt is stated to improve theeffectiveness of the antibacterial. All prior art references areincluded herein in total by reference.

It has now been found that the bioavailability and effectiveness of theantibacterial can be improved significantly having the antibacterial inthe form of a microemulsion. This allows for the antibacterial to bemore effectively deposited on the surfaces of the mouth.

It is therefore an object of the present invention to provide improvedproducts containing antibacterial agents.

It is a further object of the present invention to provide moreeffective products for treating diseases of the oral cavity.

It is still a further objective to provide methods for treating diseasesof the oral cavity.

These and other objects will become readily apparent from the disclosurewhich follows.

All percentages and ratios used herein are by weight unless otherwisespecified. Also, all measurements referred to herein are made at 25° C.in the composition unless otherwise specified.

SUMMARY OF THE INVENTION

The present invention, in certain aspects, embraces compositions havinga water-insoluble noncationic antibacterial agent in a microemulsion.

The present invention also encompasses a method for treating diseases ofthe oral cavity using the specified compositions.

By "oral compositions" as used herein means a product which in theordinary course of usage is not intentionally swallowed for purposes ofsystemic administration of particular therapeutic agents, but is ratherretained in the oral cavity for a time sufficient to contactsubstantially all of the dental surfaces and/or oral tissues forpurposes of oral activity.

By "safe and effective amount" as used herein means sufficient amount ofmaterial to provide the desired benefit while being safe to the hard andsoft tissues of the oral cavity.

By the term "comprising", as used herein, is meant that variousadditional components can be conjointly employed in the compositions ofthis invention as long as the listed materials perform their intendedfunctions.

By the term "carrier", as used herein, is meant a suitable vehicle whichis pharmaceutically acceptable and can be used to apply the presentcompositions in the oral cavity.

DETAILED DESCRIPTION OF THE INVENTION

The present invention in a certain aspect involves forming amicroemulsion of water-insoluble, noncationic antibacterials. Theessential and optional components of the compositions. The compositionsof this invention are preferably substantially free of potassium ions(e.g. less than about 0.001% potassium ions).

Antibacterial Agents

Given below are examples of antibacterial agents useful in the processof the present invention which are water insoluble and noncationic.

Halogenated Diphenyl Ethers

2,4,4'-trichloro-2-hydroxy-diphenyl ether (Triclosan)2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Phenolic Compounds (including phenol and its homologs, mono- andpoly-alkyl and aromatic halophenols, resorcinol and its derivatives,bisphenolic compounds and halogenated salicylanilides).

    ______________________________________                                        Phenol and its Homologs                                                       Phenol                                                                        2 Methyl         Phenol                                                       3 Methyl         Phenol                                                       4 Methyl         Phenol                                                       4 Ethyl          Phenol                                                       2,4-Dimethyl     Phenol                                                       2,5-Dimethyl     Phenol                                                       3,4-Dimethyl     Phenol                                                       2,6-Dimethyl     Phenol                                                       4-n-Propyl       Phenol                                                       4-n-Butyl        Phenol                                                       4-n-Amyl         Phenol                                                       4-tert-Amyl      Phenol                                                       4-n-Hexyl        Phenol                                                       4-n-Heptyl       Phenol                                                       Mono- and Poly-Alkyl and Aromatic Halophenols                                 p-Chlorophenol                                                                Methyl           p-Chlorophenol                                               Ethyl            p-Chlorophenol                                               n-Propyl         p-Chlorophenol                                               n-Butyl          p-Chlorophenol                                               n-Amyl           p-Chlorophenol                                               sec-Amyl         p-Chlorophenol                                               n-Hexyl          p-Chlorophenol                                               Cyclohexyl       p-Chlorophenol                                               n-Heptyl         p-Chlorophenol                                               n-Octyl          p-Chlorophenol                                               o-Chlorophenol                                                                Methyl           o-Chlorophenol                                               Ethyl            o-Chlorophenol                                               n-Propyl         o-Chlorophenol                                               n-Butyl          o-Chlorophenol                                               n-Amyl           o-Chlorophenol                                               tert-Amyl        o-Chlorophenol                                               n-Hexyl          o-Chlorophenol                                               n-Heptyl         o-Chlorophenol                                               o-Benzyl         p-Chlorophenol                                               o-Benxyl-m-methyl                                                                              p-Chlorophenol                                               o-Benzyl-m, m-dimethyl                                                                         p-Chlorophenol                                               o-Phenylethyl    p-Chlorophenol                                               o-Phenylethyl-m-methyl                                                                         p-Chlorophenol                                               3-Methyl         p-Chlorophenol                                               3,5-Dimethyl     p-Chlorophenol                                               6-Ethyl-3-methyl p-Chlorophenol                                               6-n-Propyl-3-methyl                                                                            p-Chlorophenol                                               6-iso-Propyl-3-methyl                                                                          p-Chlorophenol                                               2-Ethyl-3,5-dimethyl                                                                           p-Chlorophenol                                               6-sec-Butyl-3-methyl                                                                           p-Chlorophenol                                               2-iso-Propyl-3,5-dimethyl                                                                      p-Chlorophenol                                               6-Diethylmethyl-3-methyl                                                                       p-Chlorophenol                                               6-iso-Propyl-2-ethyl-3-methyl                                                                  p-Chlorophenol                                               2-sec-Amyl-3,5-dimethyl                                                                        p-Chlorophenol                                               2-Diethylmethyl-3,5-dimethyl                                                                   p-Chlorophenol                                               6-sec-Octyl-3-methyl                                                                           p-Chlorophenol                                               p-Bromophenol                                                                 Methyl           p-Bromophenol                                                Ethyl            p-Bromophenol                                                n-Propyl         p-Bromophenol                                                n-Butyl          p-Bromophenol                                                n-Amyl           p-Bromophenol                                                sec-Amyl         p-Bromophenol                                                n-Hexyl          p-Bromophenol                                                cyclohexyl       p-Bromophenol                                                o-Bromophenol                                                                 tert-Amyl        o-Bromophenol                                                n-Hexyl          o-Bromophenol                                                n-Propyl-m,mDimethyl                                                                           o-Bromophenol                                                2-Phenyl Phenol                                                               4-Chloro-2-methyl phenol                                                      4-Chloro-3-methyl phenol                                                      4-Chloro-3,5-dimethyl phenol                                                  2,4-dichloro-3,5-dimethylphenol                                               3,4,5,6-terabromo-2-methylphenol                                              5-methyl-2-pentylphenol                                                       4-isopropyl-3-methylphenol                                                    5-Chloro-2-hydroxydiphenylmethane                                             Resorcinol and its Derivatives                                                Resorcinol                                                                    Methyl           Resorcinol                                                   Ethyl            Resorcinol                                                   n-Propyl         Resorcinol                                                   n-Butyl          Resorcinol                                                   n-Amyl           Resorcinol                                                   n-Hexyl          Resorcinol                                                   n-Heptyl         Resorcinol                                                   n-Octyl          Resorcinol                                                   n-Nonyl          Resorcinol                                                   Phenyl           Resorcinol                                                   Benzyl           Resorcinol                                                   Phenylethyl      Resorcinol                                                   Phenylpropyl     Resorcinol                                                   p-Chlorobenzyl   Resorcinol                                                   5-Chloro                                                                      2,4-Dihydroxydiphenyl Methane                                                 4'-Chloro                                                                     2,4-Dihydroxydiphenyl Methane                                                 5-Bromo                                                                       2,4-Dihydroxydiphenyl Methane                                                 4'-Bromo                                                                      2,4-Dihydroxydiphenyl Methane                                                 Bisphenolic Compounds                                                         2,2'-methylene bis (4-chlorophenol)                                           2,2'-methylene bis (3,4,6-trichlorophenol)                                    2,2'-methylene bis (4-chloro-6-bromophenol)                                   bis (2-hydroxy-3,5-dichlorophenyl) sulphide                                   bis (2-hydroxy-5-chlorobenzyl) sulphide                                       Halogenated Salicylanilides                                                   4',5-dibromosalicylanilide                                                    3,4',5-trichlorosalcylanilide                                                 3,4',5-tribromosalicylanilide                                                 2,3,3',5-tetrachlorosalicylanilide                                            3,3',5-trichlorosalicylanilide                                                3,5-dibromo-3'-trifluoromethyl salicylanilide                                 5-n-octanoyl-3'-trifluoromethyl salicylanilide                                3,5-dibromo-4'-trifluoromethyl salicylanilide                                 3,5-dibromo-3'-trifluoromethyl salicylanilide                                 (Fluorophene)                                                                 Benzoic Esters                                                                p-Hydroxybenzoic Acid                                                         Methyl           p-Hydroxybenzoic Acid                                        Ethyl            p-Hydroxybenzoic Acid                                        Propyl           p-Hydroxybenzoic Acid                                        Butyl            p-Hydroxybenzoic Acid                                        Halogenated Carbanilides                                                      3,4,4'-trichlorocarbanilide                                                   3-trifluoromethyl-4,4'-dichlorocarbanilide                                    3,3',4-trichlorocarbanilide                                                   ______________________________________                                    

The antibacterial agent is present in the oral composition prepared inan effective antiplaque amount, typically about 0.01-5% by weight,preferably about 0.03-1%. The antibacterial agent is substantiallywater-insoluble, meaning that its solubility is less than about 1% byweight in water at 25° C. and may be even less than about 0.1%. If anionizable group is present solubility is determined at a pH at whichionization does not occur.

Surfactants

The surfactants useful in the compositions of this invention includemany different surfactants. Suitable surfactants include any which arereasonably stable and function over a wide pH range. Included arenon-soap anionic, nonionic, cationic, zwitterionic and amphotericorganic synthetic surfactants. Many of these are disclosed by Gieseke etal. in U.S. Pat. No. 4,051,234, Sep. 27, 1988 incorporated herein intotal by reference.

Preferred surfactants include alkyl sulfates. The surfactant isgenerally present at a level of from about 0.2% to about 7% preferablyfrom about 0.6% to about 4.0%.

Water

Water is also present in the compositions of this invention. Wateremployed in the preparation of commercially suitable compositions shouldpreferably be deionized and free of organic impurities. Water generallycomprises from about 10% to 50%, preferably from about 20% to 40%, byweight of the toothpaste compositions herein while mouthwashes containfrom about 40% to about 95%, preferably 50-80%. These amounts of waterinclude the free water which is added plus that which is introduced withother materials as with sorbitol.

Solvent

A solvent is present in the compositions of the present invention. Thesolvent is used to solubilize the antibacterial and can be any number ofagents.

Preferred agents include flavor oils such as those mentionedsubsequently or agents such as polyethylene glycols, preferably thosehaving molecular weights of from about 200 to about 600, propyleneglycol, dipropylene glycol, methyl cellosolve, ethyl cellosolve, oliveoil, castor oil, amylacetate, ethyl acetate, glyceryl tristearate,benzyl benzoate and mixtures thereof. The solvent is used generally inan amount of from about 1 to about 10%, preferably from about 2 to about6%.

The antibacterial (e.g. triclosan) surfactant and solvent aggregates, asstated hereinbefore, are in the form of a microemulsion. Microemulsionsare defined as having emulsified particles of from about 10 nm to about250 nm in diameter. See L. M. Prince (Editor) (1977) Microemulsions andTheory, Academic Press, New York, incorporated herein by reference. Themicroemulsions are preferably characterized not only in terms ofparticle size but also having the maximum deliverable antibacterial.This is obtained by adhering to the following equation: ##EQU1## wherethe microemulsion forms and the compositions having a minimum amount ofsolubilizer. The life-time of supersaturated antibacterial solutiongenerated from the microemulsion upon brushing must be much longer thanthe brushing time. This is obtained by the thickener in the composition.

Optional Components

The compositions of the present invention may contain in addition to theabove-listed components many others which will be somewhat dependent onthe type of composition (mouthwashes, toothpastes, topical gels,prophylaxis pastes and the like). Toothpastes and mouthwashes are thepreferred systems with toothpastes being the most preferred.

Toothpastes contain as a major component an abrasive. The abrasivepolishing material contemplated for use in the present invention can beany material which does not excessively abrade dentin. These include,for example, silicas including gels and precipitates, calcium carbonate,dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalciumphosphate, calcium polymetaphosphate, insoluble sodiumpolymetaphosphate, hydrated alumina, and resinous abrasive materialssuch as particulate condensation products of urea and formaldehyde, andothers such as disclosed by Cooley et al. in U.S. Pat. No. 3,070,510,Dec. 25, 1962, incorporated herein by reference. Mixtures of abrasivesmay also be used.

Silica dental abrasives, of various types, can provide the uniquebenefits of exceptional dental cleaning and polishing performancewithout unduly abrading tooth enamel or dentin. Silica abrasivematerials are also exceptionally compatible with sources of solublefluoride and other ion sources. For these reasons they are preferred foruse herein.

The silica abrasive polishing materials useful herein, as well as theother abrasives, generally have an average particle size ranging betweenabout 0.1 and 30 microns, preferably 5 and 15 microns. The silicaabrasive can be precipitated silica or silica gels such as the silicaxerogels described in Pader et al., U.S. Pat. No. 3,538,230, issued Mar.2, 1970 and DiGiulio, U.S. Pat. No. 3,862,307, Jun. 21, 1975, bothincorporated herein by reference. Preferred are the silica xerogelsmarketed under the tradename "Syloid" by the W. R. Grace & Company,Davison Chemical Division. Preferred precipitated silica materialsinclude those marketed by the J. M. Huber Corporation under thetradename, "Zeodent", particularly the silica carrying the designation"Zeodent 119". These silica abrasive are described in U.S. Pat. No.4,340,583, Jul. 29, 1982, incorporated herein by reference.

The abrasive in the dentifrice compositions described herein is presentat a level of from about 6% to about 70%, preferably from about 15% toabout 30% when the dentifrice is a toothpaste.

Flavoring agents, as was noted earlier, can also be added to thedentifrice and other compositions of the present invention. Suitableflavoring agents include oil of wintergreen, oil of peppermint, oil ofspearmint, oil of sassafras, and oil of clove. Sweetening agents arealso useful and include aspartame, acesulfame, saccharin, dextrose,levulose and sodium cyclamate. Flavoring and sweetening agents aregenerally used in the compositions herein at levels of from about 0.005%to about 2% by weight and may be used as a solvent for theantibacterials hereinbefore indicated.

In preparing toothpastes, it is necessary to add some thickeningmaterial to provide a desirable consistency. Preferred thickening agentsare carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and watersoluble salts of cellulose ethers such as sodium carboxymethyl celluloseand sodium carboxymethyl hydroxyethyl cellulose. Natural gums such asgum karaya, gum arabic, and gum tragacanth and polysaccharide gums suchas xanthan gum can also be used. Colloidal magnesium aluminum silicateor finely divided silica can be used as part of the thickening agent tofurther improve texture. Thickening agents in a combined amount from0.5% to 5.0% by weight of the total composition may be used.

It is also desirable to include a humectant in a toothpaste to keep itfrom hardening. Suitable humectants include glycerin, sorbitol, andother edible polyhydric alcohols at a level of from about 10% to about70%.

Another preferred embodiment of the present invention is a mouthwashcomposition. Mouthwashes generally comprise from about 20:1 to about 2:1of a water/ethyl alcohol solution and preferably other ingredients suchas flavor, sweeteners, humectants and sudsing agents such as thosedescribed above. The humectants, such as glycerin and sorbitol give amoist feel to the mouth. Generally, on a weight basis the mouthwashes ofthe invention comprise 5% to 60% (preferably 10% to 25%) ethyl alcohol,0% to 20% (preferably 5% to 20%) of a humectant, 0% to 2% (preferably0.01% to 0.15%) emulsifying agent, 0% to 0.5% (preferably 0.005% to0.06%) sweetening agent such as saccharin, 0% to 0.3% (preferably from0.03% to 0.3%) flavoring agent, and the balance water.

The pH of the present compositions and/or its pH in the mouth can be anypH which is safe for the mouth's hard and soft tissues. Such pH's aregenerally from about 3 to about 10, preferably from about 4 to about 9.

Another optional component of the compositions of this invention is ananionic polycarboxylate. The anionic polymeric polycarboxylatesoptionally but preferably employed herein are well known, being employedin the form of their free acids or partially or preferably fullyneutralized water soluble alkali metal (e.g. preferably sodium) orammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydrideor acid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether (methoxyethylene) having a molecularweight (M.W.) of about 30,000 to about 1,000,000. These copolymers areavailable for example as Gantrez (AN 139(M.W. 500,000), A.N. 119 (M.W.250,000) and preferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAFCorporation.

Other operative polymeric polycarboxylates include those such as the 1:1copolymers of maleic anhydride with ethyl acrylate, hydroxyethylmethacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter beingavailable for example as Monsanto EMA No. 1103, M.W. 10,000 and EMAGrade 61, and 1:1 copolymers of acrylic acid with methyl or hydroxyethylmethacrylate, methyl or ethyl acrylate, isobutyl vinyl ether orN-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred to U.S. Pat. Nos. 4,138,477 and 4,183,914, incorporated hereinby reference, include copolymers of maleic anhydride with styrene,isobutylene or ethyl vinyl ether, polyacrylic, polyitaconic andpolymaleic acids, and sulfoacrylic oligomers of M.W. as low as 1,000available as Uniroyal ND-2.

Suitable generally are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility.

Also useful herein are carboxyvinyl polymers, referred to herein earlieras suitable binders, disclosed as toothpaste components in U.S. Pat. No.3,980,767 issued Sep. 14, 1976 to Choun et al., U.S. Pat. No. 3,935,306issued Jan. 27, 1976 to Roberts et al., U.S. Pat. No. 3,919,409 issuedNov. 11, 1975 to Peria et al., U.S. Pat. No. 3,911,904 issued Oct. 7,1975 to Harrison, and U.S. Pat. No. 3,711,604 issued Jan. 16, 1973 toColodney et al. They are commercially available for example under thetrademarks Carbopol 934, 940, 941 and 956 of B. F. Goodrich, theseproducts consisting essentially of a colloidally water-soluble polymerof polyacrylic acid crosslinked with from about 0.75% to about 2.0% ofpolyallyl sucrose or polyallyl pentaerythritol as crosslinking agent.

The synthetic anionic polymeric polycarboxylate component is mainly ahydrocarbon with optional halogen and O-containing substituents andlinkages as present in for example ester, ether and OH groups, and whenpresent is generally employed in the instant compositions in approximateweight amounts of 0.05 to 3%, preferably 0.05 to 2%, more preferably 0.1to 2%.

Another optional component is a fluoride ion source. The sources offluoride ions, or fluoride-providing compounds, useful according to thisinvention are well known in the art as anticaries agents andpyrophosphatase inhibitors and also act as such agents in the practiceof this invention. These compounds may be slightly soluble in water ormay be fully water-soluble. They are characterized by their ability torelease fluoride ions in water and by freedom from undesired reactionwith other compounds of the oral preparation. Among these materials areinorganic fluoride salts, such as soluble alkali metal, alkaline earthmetal salts, for example, sodium fluoride, barium fluoride, sodiumfluorsilicate, ammonium fluorosilicate, sodium fluorozirconate, sodiummonofluorophosphate, aluminum mono- and di-fluorophosphate, andfluorinated sodium calcium pyrophosphate. Alkali metal and tinfluorides, such as sodium and stannous fluorides, sodiummonofluorophosphate (MFP) and mixtures thereof, are preferred.

The amount of fluoride-providing compound is dependent to some extentupon the type of compound, its solubility, and the type of oralpreparation, but it must be a nontoxic amount, generally about 0.005 toabout 3.0% in the preparation. In a dentifrice preparation, e.g. dentalgel, toothpaste (including cream), an amount of such compound whichreleases up to about 5,000 ppm of F ion by weight of the preparation isconsidered satisfactory. Any suitable minimum amount of such compoundmay be used, but it is preferable to employ sufficient compound torelease about 300 to 2,000 ppm, more preferably about 800 to about 1,500ppm of fluoride ion. Typically, in the cases of alkali metal fluoridesand stannous fluoride, this component is present in an amount up toabout 2% by weight, based on the weight of the preparation, andpreferably in the range of about 0.05% to 1%. In the case of sodiummonofluorophosphate, the compound may be present in an amount of about0.1-3%, more typically about 0.76%.

Still another optional component for use in the compositions is ananticalculus agent. These agents include any which are effective againstcalculus such as pyrophosphate salts as disclosed in U.S. Pat. No.4,515,772, May 7, 1985 incorporated herein by reference. The preferredagents are mono, di, tri and tetra alkali metal and ammoniumpyrophosphate. Such agents are used in amounts sufficient to reducecalculus. These amounts are preferably in an amount of at least about 1%P₂ O₇, most preferably at least about 1.3%, most preferably at leastabout 1.5%.

Other anticalculus agents are metal ions such as zinc disclosed in U.S.Pat. No. 4,022,880, May 10, 1977 to Vinson incorporated herein byreference. Still others are polymers such as those described in U.S.Pat. No. 4,661,341, Apr. 28, 1987 to Benedict and U.S. Pat. No.3,429,963, Feb. 25, 1969 to Shedlovsky, both of which are incorporatedherein by reference. Such metals are used in an amount of from about0.01% to about 5%, preferably about 0.1% to about 2%, while suchpolymers are used in amounts of from about 0.1% to about 10%, preferablyfrom about 0.5% to about 5%.

Given below are non-limiting examples which illustrate the compositionsof the present invention.

Method of Manufacture

The compositions of the present invention can be prepared using themethod described following the Examples.

Composition Use

The present invention in its method aspect involves applying to the oralcavity safe and effective amounts of the antimicrobial. Generally,amounts of at least about 0.001 g of the antimicrobial is effective.

EXAMPLES I-IV

Given below are four examples of compositions which are of the presentinvention.

    ______________________________________                                        Component    (I)     (II)    (III) (IV)  (V)                                  ______________________________________                                        Water        20.518  20.518  14.069                                                                              11.165                                                                              20.618                               Sorbitol (70%)                                                                             26.600  26.583  32.000                                                                              57.652                                                                              26.600                               Glycerin     8.000   8.000   8.000 --    8.000                                Sodium fluoride                                                                            0.243   0.243   0.321 0.243 0.243                                Sodium acid  1.220   1.220   1.220 --    1.220                                pyrophosphate                                                                 Tetrasodium  3.580   3.580   3.580 --    3.580                                pyrophosphate                                                                 Monosodium   --      --      --    0.590 --                                   phosphate                                                                     Trisodium phosphate                                                                        --      --      --    1.450 --                                   Saccharin    0.470   0.470   0.300 0.300 0.470                                FD&C Blue No. 1                                                                            --      --      --    0.050 0.400                                Titanium dioxide                                                                           0.500   0.500   0.700 0.525 --                                   Flavor       1.100   0.900   0.970 0.970 1.100                                PEG-300      4.000   4.000   4.000 --    4.000                                Triclosan    0.280   0.450   0.280 0.280 0.280                                Sodium alkyl 6.000   6.000   6.000 6.000 6.000                                sulfate (27.9%)                                                               Silica       20.300  20.300  22.000                                                                              20.000                                                                              20.300                               Xanthan gum  0.600   0.600   0.500 0.475 0.600                                Carbomer 956 0.200   0.200   0.250 0.300 0.200                                             100.000 100.000 100.000                                                                             100.000                                                                             100.000                              ______________________________________                                    

The above compositions are prepared by making a series of premixes andcombining them in a specified order.

1. Premix one consists of water, sorbitol, sodium fluoride, sodiumsaccharin, sodium acid pyrophosphate and other optional material whichare present.

2. Premix two consists of glycerin and tetrasodium pyrophosphate.

3. Premix three consists of sodium alkyl sulfate solution.

4. Premix four consists of the flavor, polyethylene glycol andtriclosan.

5. Premix five consists of titanium dioxide, silica, Carbopol andxanthan gum.

All premixes are thoroughly mixed and premix four is mixed for a timesufficient to fully solubilize the triclosan. The premixes are mixedtogether in the order given (i.e. premix two is mixed with premix one,then premix three is added to the mixture of one and two, etc.). Whenpremix four is mixed with the previously mixed premixes, the result ismixed for a time sufficient to ensure that the particle size of thetriclosan, flavor and surfactant aggregates is less than about 12nanometers in diameter by quasielastic light scattering analysis.

What is claimed:
 1. Aqueous oral toothpaste compositions comprising asoluble fluoride ion source, a non-cationic, water-insolubleantibacterial agent, a solvent for said agent, a surfactant and waterand wherein said antibacterial agent is in the form of a microemulsionand wherein said composition is substantially free of potassium ions. 2.A composition according to claim 1 wherein said solvent is a flavor oil.3. A composition according to claim 1 wherein said solvent is a glycol.4. A composition according to claim 1 wherein said solvent is acombination of flavoring oils and glycols.
 5. A composition according toclaim 4 wherein said toothpaste contains an abrasive.
 6. A compositionaccording to claim 5 wherein said toothpaste also contains triclosan asthe antibacterial agent and the ratio of surfactant to antibacterialplus flavor is equal to or greater than the critical point where themicroemulsion of the antibacterial will form.
 7. A process for treatingdiseases of the oral cavity by applying to said cavity an effectiveamount of a composition made according to claim
 1. 8. A process fortreating diseases of the oral cavity by applying to said cavity aneffective amount of a composition made according to claim 6.